Real-World Findings on Incidence of Adverse Events Highlighted for JAK Inhibitors

Real-world data suggest Janus kinase (JAK) inhibitors, especially upadacitinib, baricitinib, and abrocitinib, have a low incidence of serious adverse events in patients with atopic dermatitis and alopecia areata.1

These results represent the conclusion of a recent systematic review and meta-analysis of 43 studies, authored by such individuals as Xinghua Gao, MD, PhD, from the department of dermatology at The First Hospital of China Medical University in Shenyang, China.

Several reviews of available randomized controlled trials (RCTs) related to the safety and effectiveness of JAK inhibitors in inflammatory skin diseases had been published before this review.2 However, Gao and coauthors highlighted that the safety of these studies’ implementation in real-world settings was not clear.

“Considering that several real-world studies focusing on oral JAK inhibitors for the treatment of inflammatory skin diseases have been published in recent years, this study aims to explore the safety of oral JAK inhibitors with inflammatory skin diseases in real-world patients by conducting a meta-analysis of real-world studies,” Gao et al wrote.1

Review and Findings

Six databases, including Embase, MEDLINE (via PubMed), Web of Science, Wanfang Data Knowledge Service Platform, the China Biomedical Literature Database, and the China National Knowledge Infrastructure, were used for a literature search by the investigators. The team looked at research published from database inception through March 2024, using search terms such as "Vitiligo," “Alopecia Areata,” “Atopic Dermatitis,” and “Janus Kinase Inhibitors.”

The studies were screened by 2 independent reviewers, with such research including real-world evidence involving individuals with inflammatory skin diseases treated with baricitinib, abrocitinib, ritlecitinib, or upadacitinib. Gao and colleagues highlighted pooled incidence rates of serious infections, major adverse cardiovascular events (MACE), malignancies, death, thromboembolism, tuberculosis, hepatitis B, and herpesvirus infections. Result consistency was also evaluated through various means.

The investigative team removed 1871 dupilicates from the 6089 initial records, and they excluded 4052 publications deemed irrelevant to their review. The 157 articles remaining in this list underwent full-text review, with 41 studies determined by Gao et al to be eligible. As a pair of these studies reported information for more than 1 JAK inhibitor, they were treated as separate analyses, providing 43 studies for the meta-analysis.

These data originated from 13 countries, primarily China and Italy. No eligible studies focusing on vitiligo and most of these analyses provided data on atopic dermatitis. Among the list of JAK inhibitors, the investigators found upadacitinib to be most frequently reported, followed by baricitinib and abrocitinib. The team further concluded that ritlecitinib did not have enough real-world data.

Sample sizes were identified as generally small, with Gao and coauthors noting fewer than 100 subjects in most reports, and only 4 studies exceeding this number. The largest study in the investigators' review had enrolled 325 patients. Follow-up durations ranged from 8 - 72 weeks, with 12-week studies shown to be the most common. This was followed by 16- and 24-week studies. A single study focused exclusively on adolescents, while none specifically examined elderly patients.

Across the 43 studies (totaling 2002 patients; 35 on atopic dermatitis and 8 on alopecia areata), the investigative team identified safety outcomes for MACE, thromboembolism, cancer, serious infections, and mortality were reported. A single upadacitinib study in atopic dermatitis was noted by Gao et al as having described a single case of acute myocardial infarction. There were 3 upadacitinib studies which collectively reported 5 thromboembolic events. Specifically, 2 studies noted a single event each, and 1 study reported 3 events.

A separate investigation involving atopic dermatitis patients treated with upadacitinib, baricitinib, and abrocitinib highlighted 4 serious infections; however, drug-specific data were not shown to be available for individual analysis. There were 2 upadacitinib studies in atopic dermatitis which highlighted 2 cases of malignancy, and no deaths were recorded in any of the 43 studies.

Herpesvirus outcomes were also described: 19 studies (1,291 patients; 18 atopic dermatitis and 1 alopecia areata) provided data on herpes simplex. They found 17 studies (1181 patients, all atopic dermatitis) reported herpes zoster infections. There were no adverse events related to hepatitis B or tuberculosis identified by Gao and colleagues in any included research.

“This study, in our knowledge, is the first systematic review that analyses the safety of oral JAK inhibitors for inflammatory skin diseases in the real world,” the investigative team wrote.1 “...Although this study could not provide definitive conclusions due to limited data, we believe it is still informative and valuable for clinical practice.”

References

1. H Liu, L Zhang, H Zhang, et al. Safety of Oral JAK Inhibitors in Inflammatory Skin Diseases: A Systematic Review and Meta-Analysis of 43 Real-World Studies. Journal of Evidence-Based Medicine (2025): e70076. https://doi.org/10.1111/jebm.70076.

2. Liu M, Gao Y, Tian J, et al. Janus Kinase Inhibitors for Alopecia Areata: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2023 Jun 1;6(6):e2320351. doi: 10.1001/jamanetworkopen.2023.20351. PMID: 37368402; PMCID: PMC10300710.